Stroke is an increasingly recognized cause of childhood disability, occurring in as many as 13 per 100,000 children per year. Despite improved recognition, our understanding of the pathophysiology of this disease remains limited. A better understanding could improve our care of these children, and also shed light on non-atherosclerotic mechanisms of stroke applicable to both children and adults. Infection may be an important risk factor for childhood stroke, either due to systemic effects of inflammatory mediators causing a relatively pro-thrombotic state, or by direct or indirect effects on blood vessels through a variety of mechanisms. The overall goal of this project is explore the role of infection in childhood stroke, and thereby improve our understanding of the mechanisms underlying this disease. The Specific Aims of the study are: 1) to determine whether infections (recent febrile infection, severe acute infections such as meningitis and remote chicken pox) are risk factors for first childhood stroke; 2) to determine whether a history of infection prior to a first stroke predicts stroke recurrence, and 3) to determine whether vaccinations against varicella-zoster virus, influenza virus and bacterial etiologies of meningitis are protective against childhood stroke. We propose a case-control study within the well-defined population of approximately 1 million children enrolled in Kaiser Permanente Medical Care Program (KPMCP), a health maintenance organization including 16 hospitals and 36 out-patient facilities in Northern California. We will include as cases all children with stroke over a 17 year time period (1993 to 2009); controls will be randomly selected from the KPMCP population and matched for age. Exposure history will be measured through review of electronic and traditional medical records, and by telephone interview of subjects or their surrogates. Public Health Relevance: This study will improve our understanding of why children have strokes, an important cause of life-long physical and mental disability that tends to occur in the very youngest of children, those in the first year of life. Understanding why strokes occur in children is the first step towards designing effective methods of preventing stroke.